Detemir for Obesity

(IDIOM Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University

Must be taking: Metformin, Sitagliptin, Thiazolidinediones

Must not be taking: Steroids, Appetite suppressants

Disqualifiers: Cardiovascular disease, Substance abuse, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how insulin detemir affects weight, brain function, mood, and heart disease risk factors in people with obesity. Participants will either follow a low-calorie diet alone or combine it with insulin detemir treatment to observe how these approaches influence brain areas related to food enjoyment. It suits adults with obesity who have stable weight and manage type 2 diabetes with certain medications. As an unphased trial, this study offers a unique opportunity to contribute to understanding the broader impacts of insulin detemir on health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants can be on certain diabetes medications like metformin, sitagliptin, or thiazolidines. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that insulin detemir is generally safe for use. Studies indicate that people taking insulin detemir experience fewer cases of low blood sugar (hypoglycemia) compared to those using other types of insulin, which is important because low blood sugar can be dangerous.

Additionally, insulin detemir is associated with less weight gain than other insulin treatments. One study found that people using insulin detemir even lost a small amount of weight, while those on another insulin gained weight. This makes insulin detemir a potentially better choice for those concerned about weight gain.

Overall, these findings suggest that insulin detemir is safe and well-tolerated, offering benefits such as reducing the risk of low blood sugar and having less impact on weight. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for obesity focus on lifestyle changes or medications that suppress appetite or inhibit fat absorption. But insulin detemir works differently, targeting the brain's dopamine pathways, which are linked to reward and motivation. This approach aims to restore brain dopamine neurotransmission, potentially influencing mood, cognitive function, and weight loss. Researchers are excited about insulin detemir because it could offer a novel way to address obesity by modifying brain function rather than just managing weight through traditional means.

What evidence suggests that insulin detemir could be an effective treatment for obesity?

Research has shown that insulin detemir, which participants in this trial may receive, can manage weight better than some older insulin types. One study found that people using insulin detemir lost about 0.69 kg, while those using NPH insulin gained 1.7 kg. This suggests insulin detemir might aid in weight control. It also helps achieve blood sugar goals with less weight gain. The evidence supports its potential to help people with obesity manage their weight. ^{1 6 7 8 9}

Who Is on the Research Team?

Kevin D Niswender, MD/PhD

Principal Investigator

Vanderbilt University

Are You a Good Fit for This Trial?

Adults aged 31-60 with stable obesity (BMI of 30-49), type 2 diabetes not on insulin, and a weight under 350lbs can join. They must have maintained their weight recently, be willing to follow diet plans, and avoid certain substances before visits. Those with significant health issues or conditions that affect study participation are excluded.

Inclusion Criteria

Stable body weight during the previous 3 months with a less than 5 pounds self -reported weight change

Informed consent obtained before any trial-related activities

Age at study entry is between 31-60 years of age

Exclusion Criteria

Dietary supplements of such as EPA, DHA or omega-3 fatty acids.

Previous surgery for weight loss

Any tobacco use in last 3 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomized into two groups: one receiving a low-calorie diet and insulin detemir, and the other receiving only a low-calorie diet. The treatment involves insulin detemir administration and dietary management.

24 weeks

Weekly visits (in-person and virtual)

Inpatient Monitoring

Participants undergo inpatient visits for detailed monitoring and procedures including MRI and PET scans.

26 weeks

4 inpatient visits (2 days each at Weeks 2, 6, 16, 26)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on weight loss and dopamine signaling.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Detemir

Trial Overview The trial is testing if insulin detemir helps manage obesity when combined with a low-calorie diet compared to the diet alone. It will also look at effects on brain function, mood, heart disease risk factors through outpatient/inpatient visits involving questionnaires and scans over a period of 26 weeks.

How Is the Trial Designed?

Group I: Insulin Detemir Treatment Experimental Treatment 1 Intervention

Insulin detemir treatment: Insulin detemir will be administered subcutaneously, once daily. Dose ranges from approximately 0.1 U/kg up to 0.6 u/kg or higher. The dosing regimen will employ a strategy similar to the "303"algorithm, where, with close interaction with study personnel (rather than self-titration), bedtime insulin dosing will be titrated up by 3 units until AM fasting sugars within the prescribed protocol range are achieved (90-110 mg/dl). Subjects will have contact with study personnel on weekly basis for glycemia monitoring and adjustments. Similarly, documented hypoglycemia (blood sugars less than 70) will trigger a dose reduction, and it is expected that with weight loss, tolerable insulin dosages will drift downward. The treatment period is 24 weeks.

Group II: Comparator: No insulin Active Control 1 Intervention

The main hypothesis is that "diabetes can be changed " with early and careful insulinization capturing effects on brain function ultimately leading to weight loss. . Seek to determine in a quantitative manner whether insulin detemir restores brain dopamine neurotransmission, a control group not treated with insulin is required. The strength of this study is our ability to test the specific molecular (D2R, DAT, functional MRI responses) and integrated output (functional brain responses, mood, cognitive function, reward responses etc.) of CNS dopaminergic pathways in order to shed unprecedented light upon mechanisms of detemir action in obesity and diabetes.

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Sibutramine, a serotonin/noradrenaline reuptake inhibitor, has been shown to reduce body weight by an average of 4.45 kg compared to placebo, while also improving triglycerides and HDL cholesterol, but it may cause increased heart rate and has contraindications for patients with uncontrolled hypertension or cardiovascular issues.

Orlistat, a pancreatic lipase inhibitor, results in an average weight loss of 2.89 kg and significantly decreases waist circumference and blood pressure, but primarily causes gastrointestinal side effects and should be avoided in patients with chronic malabsorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological therapy of obesity]. Pagotto, U., Vanuzzo, D., Vicennati, V., et al.[2018]

Two new medications, phentermine/topiramate ER (Qsymia™) and lorcaserin (Belviq®), have been approved by the FDA for long-term weight management in individuals with obesity or overweight with related health issues, marking a significant advancement in obesity treatment.

The review highlights that these new drugs are either reformulations of existing medications or new approaches targeting previously established mechanisms, indicating a trend of revisiting and optimizing older treatments for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic treatment options for obesity: what is old is new again. Ryan, DH., Bray, GA.[2021]

The FDA has approved lorcaserin and the combination of phentermine and extended-release topiramate (phentermine/topiramate ER) for obesity treatment, expanding options beyond orlistat and supporting long-term weight management alongside lifestyle changes.

Phentermine/topiramate ER has been shown to result in greater weight loss compared to using phentermine or topiramate alone, and it may also improve cardiometabolic risk factors, although more long-term safety data is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. Sweeting, AN., Tabet, E., Caterson, ID., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4744774/

Weight‐sparing effect of insulin detemir - PubMed Central - NIH Insulin detemir significantly reduced body weight by 0.69 kg compared with a weight gain of 1.7 kg with NPH insulin (p < 0.001); this was consistent with the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01239550

Study Details | NCT01239550 | Insulin Detemir in Obesity ... The purpose of this study is to evaluate the effects of the medication insulin detemir on weight, brain function and mood, and on blood vessel and other ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3267521/

Insulin detemir for the treatment of obese patients with type 2 ... Results from multiple clinical trials with insulin detemir have shown that its use results in less weight gain than older types of insulin, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0889852907800065

Intensive Diabetes Therapy and Body Weight Insulin detemir is a basal insulin analog that can help patients move safely toward glycemic targets with less weight gain. This review discusses the potential ...

5. dmsjournal.biomedcentral.com dmsjournal.biomedcentral.com/articles/10.1186/1758-5996-5-56

Initiation of once daily insulin detemir is not associated with ... Overall, patients with poorly controlled T2DM achieved significant reductions in HbA1c after initiation of once-daily insulin detemir therapy, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3047990/

Critical appraisal of the safety and efficacy of insulin detemir in ... In clinical trials, insulin detemir has been characterized by consistent risk reductions in hypoglycemia, as well as reduced weight gain in comparison with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00697450

Observational Study on the Weight Effect of Insulin Detemir ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the ...

8. clinicaltrial.be clinicaltrial.be/en/details/13088?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Insulin Detemir in Obesity Management For example, an analysis of the diabetes control and complications trial (DCCT) revealed that the highest quartile of weight gain in the intensive treatment led ...

9. e-enm.org e-enm.org/journal/view.php?doi=10.3803/enm.2020.35.1.142

Comparison of the Efficacy and Safety of Insulin Detemir ... Comparison of the efficacy and safety of insulin detemir administered once daily according to two titration algorithms (3-0-3 and 2-4-6-8) in patients with ...